Cox H M, Cuthbert A W
Department of Pharmacology, University of Cambridge, U.K.
Regul Pept. 1989 Sep-Oct;26(2):127-35. doi: 10.1016/0167-0115(89)90004-9.
Vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), and helodermin stimulate electrogenic anion secretion in preparations of rat jejunum stripped of muscularis propria. Concentration-response curves to exogenously applied peptides yielded EC50 values of 12 nM, 12 nM and 100 nM for VIP, PHI and helodermin respectively. These secretory responses were most probably mediated via the same receptor population given that cross-desensitisation was observed between all 3 analogues. Four putative VIP antagonists, namely, two growth hormone releasing factors (GRF); [AcTyr1, D-Phe2]GRF-(1-29)-NH2 and [AcTyr1]hGRF-(1-40)-OH as well as [4Cl-D-Phe6,Leu17]VIP and VIP-(10-28) were tested for their ability to inhibit VIP induced electrogenic ion secretion. None of the above exhibited any intrinsic agonist activity nor were they competitive antagonists, although some inhibition was observed with [AcTyr1]hGRF-(1-40)-OH and VIP-(10-28). Their use as selective VIP antagonists is therefore limited in rat jejunal mucosa.
血管活性肠肽（VIP）、肽组氨酸异亮氨酸（PHI）和蛙皮素可刺激去除固有肌层的大鼠空肠制剂中的电生性阴离子分泌。对外源性应用的肽的浓度-反应曲线显示，VIP、PHI和蛙皮素的EC50值分别为12 nM、12 nM和100 nM。鉴于在所有三种类似物之间观察到交叉脱敏，这些分泌反应很可能是通过相同的受体群体介导的。测试了四种假定的VIP拮抗剂，即两种生长激素释放因子（GRF）；[AcTyr1, D-Phe2]GRF-(1-29)-NH2和[AcTyr1]hGRF-(1-40)-OH以及[4Cl-D-Phe6,Leu17]VIP和VIP-(10-28)抑制VIP诱导的电生性离子分泌的能力。上述物质均未表现出任何内在激动剂活性，也不是竞争性拮抗剂，尽管用[AcTyr1]hGRF-(1-40)-OH和VIP-(10-28)观察到了一些抑制作用。因此，它们作为选择性VIP拮抗剂在大鼠空肠黏膜中的应用受到限制。
